Sato H, Aoki Y
Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Japan.
Curr Drug Metab. 2002 Jun;3(3):311-9. doi: 10.2174/1389200023337603.
There is serious concern about the adverse effects of environmental pollutants on human health. Various mutagens, which pollute air, water, and food, possibly induce mutations in humans, and are suspected of causing cancer. Environmental mutagens, such as polycyclic aromatic hydrocarbons (PAH) and heterocyclic amines are known to bind to nucleotides, resulting in the formation of DNA adducts. Some DNA adducts are fixed as mutations through replication of DNA. Reactive oxygen species generated by pollutants also induce the formation of DNA adducts. DNA adducts have been detected as a marker for the exposure of humans and wild life to mutagens. Because of its high sensitivity the 32P-postlabel-thin layer chromatography (TLC) method is widely used for the analysis of DNA adducts formed by PAH and related bulky compounds. However, new systems are required for detecting mutations induced in genomic DNA in vivo to monitor environmental mutagens. Recently, transgenic animals, in which a target gene for detecting mutations is integrated, have been developed. With these transgenic animals, not only mutant frequency but mutation spectra can be determined. We review here recent advances in the detection of DNA adducts formed by environmental pollutants and their application for biological monitoring of environmental mutagens. We also discuss transgenic animals as important tools for evaluating the total mutagenic potential of environmental chemicals.
环境污染物对人类健康的不利影响引发了严重关注。各种污染空气、水和食物的诱变剂可能会在人类中诱发突变,并被怀疑会导致癌症。已知多环芳烃(PAH)和杂环胺等环境诱变剂会与核苷酸结合,导致DNA加合物的形成。一些DNA加合物通过DNA复制被固定为突变。污染物产生的活性氧也会诱导DNA加合物的形成。DNA加合物已被检测为人类和野生动物接触诱变剂的标志物。由于其高灵敏度,32P后标记薄层色谱(TLC)方法被广泛用于分析由PAH和相关大分子化合物形成的DNA加合物。然而,需要新的系统来检测体内基因组DNA中诱导的突变,以监测环境诱变剂。最近,已开发出整合了用于检测突变的靶基因的转基因动物。利用这些转基因动物,不仅可以确定突变频率,还可以确定突变谱。我们在此回顾环境污染物形成的DNA加合物检测及其在环境诱变剂生物监测中的应用的最新进展。我们还将讨论转基因动物作为评估环境化学物质总诱变潜力的重要工具。